There is sufficient evidence to confirm that olfactory and taste dysfunctions are prominent signs of COVID-19 infection. These symptoms can range from total loss (anosmia and ageusia) or partial loss (hyposmia and hypogeusia) to abnormal perception (parosmia and parageusia) and perception without stimulus (phantosmia and phantogeusia) .
Using an advanced deep neural network, the prevalence of anosmia/dysgeusia was determined to be 27.1 times in patients with COVID-19. OTD was identified as one of the most salient early features of COVID-19 infection . The frequency of reported symptoms though has varied widely across the available literature. The prevalence of OD ranges from 1.6 to 98.33%. The highest mean prevalence was recorded in the Americas (56.05%), Europe (55.44%), and the Middle East (50.42%), while in Asia and Africa, it was 28.83% and 26.5%, respectively. The prevalence of GD ranges from 1.2 to 90.3%. The mean prevalence was higher in Europe (58.6%) and the Americas (52.53%) and much lower in Asia (27.19%), the Middle East (23.23%) and Africa (22.1%) .
While some studies report a similar prevalence of both taste and smell disorders, others have shown greater variations. This may be due to the heterogeneous study designs and the diverse and subjective nature of the complaints. Studies have shown inconsistent results with regard to which sensation is affected more or if the absence of sensation is more common than reduced sensation.
The pooled proportion of patients with OD and GD was 41% and 38.2%, respectively, in one meta-analysis . Similar degrees of loss of smell (65.3%) and taste (64.3%) were reported by Alshakhs et al . OD and GD in over 80% and 90% of patients, respectively, were reported by Beltrán-Corbellini et al . On the other hand, in a large study of over 2000 patients using online questionnaires, 87% of patients had OD and 56% suffered from GD .
Klopfenstein et al. stated that 47% of their patients had anosmia and 85% had dysgeusia .
In a single-centre study, 41.7% of patients reported combined disorders of olfaction and taste, isolated OD was seen in 12.5%, and isolated GD in 14.4% . In a multicentre study, the authors found 79.3% of patients suffering from combined disturbances, but only 8.6% and 12.1% had isolated OD and GD, respectively .
Catton and Gardner observed that smell loss in the absence of taste loss was more prevalent which is supported by Lee et al. (36% more cases of smell loss without taste loss) [14, 15]. In our study, 31.3% of patients developed symptoms related to smell or taste dysfunction. Twenty-seven per cent reported GD, and 25.5% had OD. A higher proportion of patients had GD without OD than the other way around (21.53% vs 16.75%). Anosmia (19.3%) and ageusia (19.7%) were more common than partial loss (5.7% for both).
Lechien et al. reported that 85.6% of their patients had OD. Among them, 79.6% of patients were anosmic, and 20.4% had hyposmia. GD was reported in 88% of their patients . Out of 180 patients evaluated by Tipirdamaz et al., 78.6% had anosmia, and 21.4% had hyposmia .
Hyposmia (52.2%) and hypogeusia (34.5%) were more common compared to anosmia (17.7%) and ageusia (10.4%) in a study of 345 patients by Vaira et al. They also determined that in the early days of the infection, severe dysfunctions affected 70.9% of patients while in the later part (after day 10) most of the symptoms were mild to moderate .
OTD was the first symptom in 29.2% and the only one in 9.5% of the cases in a multicentric study . In another study, OD appeared before the other symptoms in 11.8% of cases .
18.1% of patients had OTD at the time of presentation in a single-centre study . OTD represented the first clinical sign of the disease in 13.6% of our patients.
Age and sex
While no significant association with age and sex was reported by Varia et al., other studies found OTD to be significantly more common in younger and female patients [13, 11, 17]. Hafez et al. reported that females had a significantly higher prevalence of OTD (p< 0.001), but there was no association with age . The higher incidence of OTD in women has been attributed to gender differences in the inflammatory response process . Contrary to their findings, our study population showed a significant association with younger age but no association with sex. Although some studies do suggest a correlation, one systematic review found no association between sensory recovery and age .
Objective testing vs subjective reporting
Thirty-eight per cent (38%) of patients with self-reported symptoms in one study had normal smell on testing and suggested that the prevalence of these complaints would be overestimated in studies based on subjective reports . Vaira et al. on the other hand found mild hyposmia in 10.7% of patients who reported no OD (p = 0.000) and 70% of patients who reported complete resolution, on testing proved to be hyposmic (p = 0.000). Similarly, among those who reported complete taste recovery, hypogeusia was detected in 28.8%. Patients who reported isolated dysfunctions of either taste or smell, on testing, were found to be hyposmic in 32.3% (p = 0.000) and hypogeusic in 22.7% (p= 0.024) of the cases, leading the authors to conclude that interview studies may be underestimating the frequency of these disorders .
Association between symptoms
Attempts have been made to quantify the relationship between olfactory and taste symptoms. Lechien et al. and Ciofalo et al. reported a significant relationship between the two (r = 0.91) (p< 0.0001) [1, 22]. Ali et al. and Catton and Gardner found a moderate correlation between the intensity of the two symptoms, while a weak correlation was demonstrated by Song et al. in a larger study population (n= 1172) [14, 23].
The ANOSVID Study found GD to persist more often in patients with persistent olfactory symptoms (p< 0.001). Asthma and cacosmia were also significantly linked with the persistence of olfactory dysfunction . Our study population showed a significant small positive relationship between OD and GD (r = 0.234, p < 0.001). There was a strong positive relationship between OTD with fever and a moderate relationship with breathing difficulty.
Effects on quality of life (QOL)
OTD affects the QOL of patients considerably, even in the absence of other symptoms. Persistent dysfunction can worsen patient well-being and may even lead to psychiatric disorders such as depression and anxiety .
A study evaluating mental health responses to OTD reported that more than 40% of their patients experienced that loss of smell made them feel isolated, 2/3rd of them had a change in dietary habits and over 1/3rd found it difficult to take part in normal daily activities. Anosmia was a trigger for loss of temper in 28.2% and dysgeusia caused an imbalance in the life of 62.1% of the patients .
After 2 weeks of testing positive, the proportion of recovered patients ranged from 25.5 to 80% [1, 11]. In a retrospective analysis using an online survey, full recovery was calculated to have a median duration of 12.5 days, with about half the patients recovering in that time .
Another study from Israel reported a median recovery from anosmia of 7.6 days (35.7% recovered) .
Lee et al. noted that it took over 3 weeks for a cohort of 3191 patients in South Korea to fully recover. The younger patients (ages 20–39) were more likely to have delayed recovery from anosmia .
Persistent OTD, even 7 months after the symptom onset, was present in 24% of patients in the study by Nguyen et al. and was more common in women (73.3%) than in men (26.7%) .
Even after 5 weeks, OD and GD continued in 37% and 7% of patients, respectively, in a smaller study sample (n= 72) . One multicentre study also reported about 56% of patients having persistent OD even after the resolution of the other symtpoms .
Cecchetto et al. reported a strong relationship between the recovery of smell and taste . Another study suggested that the association of recovery time was stronger than the correlation between the severity of these symptoms .
In our cohort, the mean duration for the recovery of taste was 15.56 days and 16.87 days for smell recovery. We found a strong, significant correlation between the recovery times of OTD and fever while only a weak and statistically insignificant correlation existed with recovery time and breathing difficulty.
In the ANOSVID Study, 85% of patients recovered from OD within 3 months, followed by a recurrence after recovery, resulting in 41% of cases having OD after more than 9 months .
ACE2 receptors are located on the olfactory and respiratory epithelium of the nasal cavity and even on the olfactory bulb . Primarily located in the motile cilia, ACE2 receptors are thought to be the site of COVID-19 viral entry .
OD in COVID-19 is thought to be due to damage to the supporting cells of the olfactory epithelium which have an abundance of ACE2 receptors. The virus attaches to these receptors and induces cell death, leaving sensory neurons vulnerable and without nutrients .
Direct infection of taste cells causing cell death or reduced secretion of neurotransmitters has been proposed as a cause for altered taste sensation [33, 34].
Viral binding to ACE2 may also lead to GD since the renin–angiotensin–aldosterone system is believed to take part in the cleaving of gustatory molecules .
GD and its improvement have been linked with the blood levels of IL-6 as well .
A strong association has been established between chemosensory dysfunctions of smell/taste and a positive COVID-19 test. Therefore, it may even serve as a preliminary tool for identifying and isolating suspected cases. OTD can help to predict clinical outcomes. Quicker recovery can indicate the resolution of viral infection .
Our study is a telephonic, subjective, self-reported assessment which is affected by recall bias, lack of accurate grading, and differentiation of true dysfunction or loss. This may lead to imprecise (over or under) reporting. Although we did try to evaluate the use of pharmaceutical interventions that can alter the progression of OTD, most patients were not able to recollect information about the medications consumed. Because there were no control groups, we could not compare the chemosensory dysfunction to its prevalence in the general population.